Comparative in vitro activities of SMT19969, a new antimicrobial agent, against Clostridium difficile and 350 gram-positive and gram-negative aerobic and anaerobic intestinal flora isolates.

Comparative in vitro activities of SMT19969, a new antimicrobial agent, against Clostridium difficile and 350 gram-positive and gram-negative aerobic and anaerobic intestinal flora isolates.
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DOI:
10.1128/aac.01136-13
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发表时间:
2013-10
影响因子:
4.9
通讯作者:
Merriam CV
Merriam CV
中科院分区:
医学2区
文献类型:
--
作者:
Goldstein EJ;Citron DM;Tyrrell KL;Merriam CV

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研究了SMT 19969(一种新型、窄谱、不可吸收的药物)对50种核糖体类型定义的艰难梭菌菌株、174种革兰氏阳性和136种革兰氏阴性肠道厌氧菌以及40种革兰氏阳性需氧菌的体外活性比较。SMT 19969对C.艰难梭菌分离株(MIC范围,0.125至0.5 μg/ml; MIC 90,0.25 μg/ml),包括核糖体型027菌株,比非达霉素(范围,0.06至1 μg/ml; MIC 90,0.5 μg/ml)低,比万古霉素或甲硝唑低2至6个稀释度。与万古霉素和甲硝唑相比,SMT 19969和非达霉素对革兰氏阴性厌氧菌,尤其是脆弱拟杆菌组物种的活性通常较低,表明SMT 19969对维持定殖抗性的正常肠道微生物群的影响较小。SMT 19969对其他革兰氏阳性厌氧菌(包括双歧杆菌、迟缓埃格菌、巨大Finegoldia magna和厌氧消化链霉菌)的活性有限,MIC 90分别为>512、>512、64和64 μg/ml。梭状芽孢杆菌属的敏感性各不相同,其中C.无毒念珠菌敏感(MIC 90,1 μg/ml); ramosum和C.产气荚膜杆菌不敏感(MIC_(90)>512 μg/ml)。抗乳酸杆菌活性(范围,0.06至>512 μg/ml; MIC 90,>512 μg/ml)与非达霉素相当,并且因物种和菌株而异。革兰氏阳性需氧球菌(金黄色葡萄球菌、粪肠球菌、大肠埃希菌);屎肠球菌和链球菌)显示出较高的SMT 19969 MIC 90值(128至>512 μg/ml)。
The comparative in vitro activity of SMT19969, a novel, narrow-spectrum, nonabsorbable agent, was studied against 50 ribotype-defined Clostridium difficile strains, 174 Gram-positive and 136 Gram-negative intestinal anaerobes, and 40 Gram-positive aerobes. SMT19969 was one dilution more active against C. difficile isolates (MIC range, 0.125 to 0.5 μg/ml; MIC90, 0.25 μg/ml), including ribotype 027 strains, than fidaxomicin (range, 0.06 to 1 μg/ml; MIC90, 0.5 μg/ml) and two to six dilutions lower than either vancomycin or metronidazole. SMT19969 and fidaxomicin were generally less active against Gram-negative anaerobes, especially the Bacteroides fragilis group species, than vancomycin and metronidazole, suggesting that SMT19969 has a lesser impact on the normal intestinal microbiota that maintain colonization resistance. SMT19969 showed limited activity against other Gram-positive anaerobes, including Bifidobacteria species, Eggerthella lenta, Finegoldia magna, and Peptostreptococcus anaerobius, with MIC90s of >512, >512, 64, and 64 μg/ml, respectively. Clostridium species showed various levels of susceptibility, with C. innocuum being susceptible (MIC90, 1 μg/ml) and C. ramosum and C. perfringens being nonsusceptible (MIC90, >512 μg/ml). Activity against Lactobacillus spp. (range, 0.06 to >512 μg/ml; MIC90, >512 μg/ml) was comparable to that of fidaxomicin and varied by species and strain. Gram-positive aerobic cocci (Staphylococcus aureus, Enterococcus faecalis, E. faecium, and streptococci) showed high SMT19969 MIC90 values (128 to >512 μg/ml).